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In 1941, Tisza immigrated to the United States and joined the faculty at the Massachusetts Institute of Technology. His research areas included theoretical physics and the history and philosophy of science, specifically on the foundation of thermodynamics and quantum mechanics. He taught at MIT until 1973.

Tisza was the author of the 1966 book, Generalized Thermodynamics. The 1982 publication, Physics as Natural Philosophy: Essays in Honor of László Tisza, was written by Tisza's colleagues and former students in honor of his 75th birthday.